Amoebozoa

Amoebozoa (from the Ancient Greek amoibe, "change" or "transformation") is a major eukaryotic supergroup and phylum comprising approximately 2,400 described extant species of amoeboid protists and slime molds (Mycetozoa). Within the deep eukaryotic tree of life, phylogenomic analyses place Amoebozoa inside the megagroup Amorphea (formerly Unikonta) as the living sister supergroup to Obazoa (the clade containing Opisthokonta: Fungi, Choanoflagellates, and Metazoa / Animals).

Crucially, not every organism that moves like an "amoeba" belongs to Amoebozoa: filose and reticulose amoebae with thread-like pseudopodia (such as Foraminifera, Radiolaria, and chlorarachniophytes) belong to the distant Rhizaria (SAR supergroup), and the brain-eating flagellate amoeba Naegleria fowleri belongs to Discoba (Excavata). True Amoebozoa are united by blunt, finger-like or sheet-like lobose pseudopodia driven by cortical actin–myosin II networks, branched tubular mitochondrial cristae, and a rich repertoire of metazoan-like cell-signaling and cytoskeletal genes.

How does a wall-less amoebozoan cell (such as Amoeba proteus, measuring up to 500–800 μm across, or Dictyostelium discoideum) crawl across a substrate at 10–300 μm/min and engulf bacterial or protozoan prey?

1. Actin Polymerization Protrusion and Actomyosin Sol–Gel Contraction: The amoeboid cytoplasm is dynamically partitioned into two interconverting physical states: an outer, stiff, cross-linked actin-filament cortex (ectoplasm / plasmagel) and an inner, fluid cytoplasmic core (endoplasm / plasmasol).
   • At the leading edge (anterior hyaline cap), extracellular chemoattractants (such as bacterial folic acid or cyclic AMP) activate Ras and Rac/Cdc42 small GTPases, which stimulate the SCAR/WAVE and Arp2/3 complexes to nucleate a dense, dendritic mesh of branched F-actin microfilaments pushing the plasma membrane forward—or alternatively, intracellular hydrostatic pressure breaks through a local weak spot in the actin cortex to inflate a hemispherical membrane bleb (Charras & Paluch, 2008).
   • At the trailing rear (uroid), RhoA/ROCK signaling activates non-muscle Myosin II bipolar minifilaments to contract the cortical actin gel, squeezing the fluid endoplasm forward into the advancing lobopodium while disassembling old actin filaments via ADF/cofilin to recycle monomeric G-actin.
2. Receptor-Mediated Phagocytosis: When a pseudopod contacts a bacterium, yeast, or ciliate, lectin and integrin-like transmembrane receptors trigger actin-cup extensions that zipper around the prey to seal it inside a phagosome, which fuses with V-ATPase-acidified lysosomes packed with pore-forming amoebapores (saposin-like peptides), cysteine proteases, and lysozymes.

Why were "slime molds" (Eumycetozoa) historically misclassified as fungi when they lack chitin cell walls (except in spore coats), lack absorptive mycelial nutrition, and are actually phagotrophic amoebae? Because when starved of bacterial prey, they undergo two contrasting transitions from single cells to macroscopic spore-dispersing fruiting bodies:

1. Cellular Slime Molds (Dictyostelium discoideum): Cyclic AMP Waves, Multicellular Slugs, and 20% Altruistic Suicide:
   • So long as soil bacteria are abundant, Dictyostelium discoideum lives as thousands of independent, solitary haploid amoebae dividing by binary fission.
   • When bacteria are exhausted and the amoebae begin to starve, pioneer cells start secreting rhythmic pulses of 3′,5′-cyclic adenosine monophosphate (cAMP) every ~6 minutes. Neighboring amoebae detect cAMP via seven-transmembrane G-protein-coupled cAMP receptors (cAR1–cAR4), crawl up the chemical gradient (chemotaxis), and relay the cAMP pulse outward—generating mesmerizing target and spiral Turing-like reaction–diffusion waves across several centimeters of soil!
   • Approximately 100,000 separate individual amoebae stream together and adhere via polymorphic cell-surface immunoglobulins (TgrB1 and TgrC1, which act as a "greenbeard" kin-recognition lock-and-key so non-relatives are excluded!) to form a cohesive, 2-mm-long multicellular migrating "slug" (pseudoplasmodium) that crawls toward light and heat without any cell fusion.
   • At the surface, the slug stands upright and executes an act of evolutionary altruism: triggered by the chlorinated alkylphenone morphogen DIF-1 (Differentiation-Inducing Factor-1), ~20% of the cells sacrifice their lives (undergoing autophagic vacuolar programmed cell death and synthesizing cellulose walls) to build a rigid, dead stalk that lifts the remaining ~80% of the cells into the air to differentiate into viable, hardy spores! (And in 2011, Debra A. Brock, Joan E. Strassmann, and David C. Queller discovered that wild Dictyostelium slugs even practice primitive agriculture: carrying live food bacteria inside their spores to "seed" new bacterial lawns wherever the spores land!).
2. Plasmodial Slime Molds (Physarum polycephalum): Giant Syncytial Shuttle Streaming and Brainless Network Computation:
   • Unlike Dictyostelium (whose aggregating cells keep their individual plasma membranes intact), when two haploid amoebae or biflagellate swarm cells of the bright-yellow plasmodial slime mold Physarum polycephalum fuse sexually, the diploid zygote undergoes repeated synchronous nuclear divisions (every ~8–10 hours) without cytokinesis.
   • The result is a macroscopic, bright-yellow, branching vascular network called a plasmodium—a single giant multinucleate cell up to 30–100 cm across containing millions of diploid nuclei streaming back and forth through tubular veins at velocities of up to 1.35 mm/second (shuttle streaming, reversing direction every ~90–120 seconds driven by peristaltic cortical actomyosin waves!).
   • Although Physarum lacks a single neuron or brain, Toshiyuki Nakagaki, Atsushi Tero, and colleagues (2000, 2010) demonstrated in Nature and Science that a Physarum plasmodium solves shortest-path labyrinth mazes and reconstructs the optimal fault-tolerant geometry of the Tokyo metropolitan rail network! When oat flakes were placed on an agar map at the exact locations of Tokyo and its 36 surrounding cities, the Physarum cell explored all paths with a sheet of cytoplasm and then selectively thickened tubes carrying high peristaltic flux while pruning redundant tubes—converging within 26 hours on a network with virtually identical transport efficiency, total length, and fault resilience to the human-engineered Tokyo railway!

How does Entamoeba histolytica kill human intestinal cells by "biting" them alive (Amoebic Trogocytosis)?

For over a century, parasitologists assumed that Entamoeba histolytica (whose Latin species name literally means "tissue-dissolving") killed human intestinal epithelial cells and lymphocytes from a distance by secreting soluble cytolytic toxins and cysteine proteases, and then phagocytosed the dead corpses. In 2014, live real-time confocal microscopy by Katherine S. Ralston, William A. Petri Jr., and colleagues revealed a startlingly different mechanism: upon adhering to a live human T-cell or enterocyte via its Gal/GalNAc lectin, Entamoeba uses actin-myosin force to bite off and swallow discrete membrane-bound mouthfuls of the living human cell (amoebic trogocytosis, from the Greek trogo, "to nibble")! After losing several bites of plasma membrane and cytoplasm, the human cell suffers lethal intracellular calcium elevation and dies—at which point the amoeba immediately loses interest and detaches from the dead corpse to attack the next living cell!

1. Nakagaki, T., Yamada, H., & Tóth, Á. (2000). Maze-solving by an amoeboid organism. Nature, 407(6803), 470. doi:10.1038/35035159
2. Eichinger, L., Pachebat, J. A., Glöckner, G., Rajandream, M.-A., Sucgang, R., Berriman, M., ... & Kuspa, A. (2005). The genome of the social amoeba Dictyostelium discoideum. Nature, 435(7038), 43–57. doi:10.1038/nature03481
3. Tero, A., Takagi, S., Saigusa, T., Ito, K., Bebber, D. P., Fricker, M. D., ... & Nakagaki, T. (2010). Rules for biologically inspired adaptive network design. Science, 327(5964), 439–442. doi:10.1126/science.1177894
4. Brock, D. A., Douglas, T. E., Queller, D. C., & Strassmann, J. E. (2011). Primitive agriculture in a social amoeba. Nature, 469(7330), 393–396. doi:10.1038/nature09668
5. Ralston, K. S., Solga, M. D., Mackey-Lawrence, N. M., Somlata, Bhattacharya, A., & Petri, W. A., Jr. (2014). Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion. Nature, 508(7497), 526–530. doi:10.1038/nature13242
6. Kang, S., Tice, A. K., Spiegel, F. W., Silberman, J. D., Pánek, T., Čepička, I., ... & Brown, M. W. (2017). Between a pod and a hard test: The deep evolution of amoebae. Molecular Biology and Evolution, 34(9), 2258–2270. doi:10.1093/molbev/msx162